tbuckley/cabot-search huggingface dataset:
Cabozantinib in combination with anti-PD1 immune checkpoint inhibitor in syngeneic tumor mouse models
Authors: S. Rolland, S.G. Klinz, F. Meyer-Losic, J. Nahkle, R. Delille, M. Hillairet de Boisferon
Journal: Annals of Oncology (2018)

Background: Cabozantinib (C) is a tyrosine kinase inhibitor against VEGFR2, RET, MET and AXL that has demonstrated clinical activity in RCC and 2L HCC and has been shown to promote an immune-permissive environment. C is undergoing clinical trials in combination with immune checkpoint inhibitors (ICI). The objectives of this preclinical study were to determine systemic cytokine profile changes induced by the combination with αPD1 and to assess cooperativity in anti-tumoral effects. Methods: Syngeneic colon (CT26, Colon38) and bladder (MBT2) tumor models were established in BALB/C, C57Bl6 or C3H/HEJ mice. C (10 or 30 mg/kg po qd) and αPD1 (10 mg/kg ip 2x weekly) were given for up to 30 days simultaneously or with a delay for αPD1, and serum was collected. Results: Serum cytokines & chemokines were assessed after coadministration of C (30 mg/kg) and αPD1 for 30 days, or when αPD1 was administered 14 days after C. VEGFA, IL3, GM-CSF, MIP1beta, IL17, CCL5, IFNγ, IL10 and IL5 were elevated in the former with a median of 72x (range 39-1207x), as compared to αPD1 or C administered alone with a median of 3.7x (1.4-135x) and 1.0x (0.5-1.9x), respectively, relative to vehicle-treated animals. Delayed treatment of αPD1 did not exhibit the same increase in analyte levels as seen with the simultaneous administration (median of 1.74x (1-9.9x). For anti-tumor efficacies, two C doses were explored in CT26 (T/C10/30 67/38% - tumor growth inhibition T/C ratios at 10 or 30 mg/kg), MBT2 (T/C10/30 37/14%) and Colon38 (T/C10/30 21/12%) models. C at 30 mg/kg led to strong anti-tumor efficacy in MBT2 and Colon38, limiting any ICI combinatorial impact to the post-treatment tumor expansion. For CT26 (30 mg/kg) and MBT2 (10 mg/kg), simultaneous dosing of C and αPD1 showed greater anti-tumor effects than single agents despite only limited effects of αPD1 alone. C + αPD1 more than doubled the treatment-specific time that tumors required to reach 1000mm3 compared to C alone. Conclusions: Together, these results indicate that simultaneous treatment of C with αPD1 lead to strong systemic increases in key cytokines & chemokines and can result in robust anti-tumor efficacy. Our results support the clinical exploration of C + ICI combinations and the potential of this TKI for use in further clinical settings. Legal entity responsible for the study: Ipsen Innovation SAS. Funding: Ipsen Innovation. Disclosure: S. Rolland, J. Nahkle, R. Delille: Employee of Ipsen. S.G. Klinz, F. Meyer-Losic: Employee and stock owner: Ipsen. All other authors have declared no conflicts of interest.
Telemetry-medical command in coronary and other mobile emergency care systems
Authors: E. L. Nagel
Journal: JAMA (1970)

By means of a telemetry-medical command system, a program based on cooperation between in-hospital physicians and mobile paramedical rescue crews, 146 consecutive victims were monitored remotely by telemetered electrocardiogram over a 24-month period. Of those successfully monitored, ventricular fibrillation or standstill was found in 15% while bradyrhythmias were found in 6%. Response time by rescue vehicle was four minutes or less in 80% of the cases. This mobile emergency care system offers advantages over new and special physician-staffed systems in that it has very fast response times, uses highly trained paramedics, possesses immediate availability, entails lower costs, permits higher utilization by applying to a greater variety of emergency conditions, and commands general community acceptance. Defibrillation of a victim outside the hospital was monitored by radio.
Altered norepinephrine turnover in the brain of rats with chronic renal failure.
Authors: R Bigazzi, E Kogosov, V M Campese
Journal: Journal of the American Society of Nephrology (1994)

Disturbances of the sympathetic nervous system have been described in chronic renal failure, but their role in the genesis and maintenance of hypertension frequently associated with this condition has not been established. The neuroadrenergic activity in brain nuclei involved in the regulation of blood pressure in uremic animals has also not been previously evaluated. In these studies, the neuroadrenergic activity was measured in the anterior, lateral, and posterior hypothalamic nuclei, in the locus coeruleus, and in the nucleus tractus solitarius of Sprague Dawley rats 5/6 nephrectomized or sham operated 4 wk before the experiments. Neuroadrenergic activity was determined by calculating norepinephrine (NE) turnover rate (in picograms per milligram per hour), 3, 6 and 12 h after inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly greater in the posterior hypothalamic nuclei (21,501 +/- 1,777 pg/mg wet wt) and in the locus coeruleus (16,152 +/- 1,114 pg/mg wet tissue) of uremic compared with control rats (12,213 +/- 1,404 and 7,991 +/- 622 pg/mg wet wt, respectively). On the other hand, the endogenous NE content of the nucleus tractus solitarius and the anterior hypothalamic nuclei did not differ between uremic and control rats. The turnover rate of NE in the posterior hypothalamic nuclei of uremic rats (2150 +/- 430 pg/mg per hour) was significantly faster (P < 0.05) than in control rats (977 +/- 244 pg/mg per hour). The turnover rate of NE in the locus coeruleus of uremic rats (2,584 +/- 323 pg/mg per hour) was also significantly faster than in control animals (400 +/- 140 pg/mg per hour; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal editors and the press
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The unusual editorials in<i>JAMA</i>by Gail McBride and Lawrence D. Grouse, MD, PhD (1981;245:375), concerning the "Ingelfinger Rule" and the "Relman Recommendation" suggest that the editors of the<i>New England Journal of Medicine (NEJM)</i>wish to become sole arbiters to decide what medical information is worthy of publication. Since these editorial policies of the NEJM were developed with the complete agreement of the Committee on Publications of the Massachusetts Medical Society, of which I was chairman during that period, responsibility for these decisions did not devolve solely on the editors. The policy of the<i>NEJM</i>in simple terms is that the value and accuracy of presentations, abstracts, and articles is impossible to determine in a few hours or days and that the public is served best by careful prepublication evaluation by appropriate experts. The<i>NEJM</i>certainly makes no claim of infallibility; however, this system of vigorous
Accidental
Authors: Jack Coulehan
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Microalbuminuria in Type I Diabetic Patients: Prevalence and Clinical Characteristics
Journal: Diabetes Care (1992)

Objective To estimate the prevalence of microalbuminuria, overnight urinary albumin excretion rate (AER) ≥30 and ≤250 μg/min, in a large sequential sample of nonhypertensive insulin-dependent (type I) diabetic patients attending hospital diabetic clinics, to identify micro- and normoalbuminuric patients in this sample for subsequent intervention and natural history follow-up studies, and to compare the clinical characteristics of the micro- and normoalbuminuric patients identified. Research Design and methods Screening was conducted in two phases. In phase 1, all eligible patients were asked to provide an early morning urine specimen for measurement of albumin concentration and albumin-creatinine ratio. In phase 2, all patients with an albumin concn ≥15 mg/L and/or an albumin-creatinine ratio ≥3.5 mg/mmol and a random sample of those with an albumin concn &amp;lt;15 mg/L and albumin-creatinine ratio &amp;lt;3.5 mg/mmol were asked to collect a timed overnight urine specimen for determination of AER. Results Among 1888 patients (16–60 yr old, diabetes onset &amp;lt;40 yr, and duration of diabetes &amp;lt;35 yr) who were screened, the prevalence of microalbuminuria was ∼3.7% (95% confidence interval (CI) 2.7–7.6%). Duration of diabetes was significantly longer in micro- than normoalbuminuric patients (20 vs. 15 yr, respectively; P &amp;lt;0.001), and in no patient with microalbuminuria was the duration of diabetes &amp;lt;5 yr. Systolic and diastolic blood pressures, higher in micro- than normoalbuminuric patients (132 vs. 122 mmHg, P &amp;lt;0.01; 77 vs. 72 mmHg, P &amp;lt;0.01), were strongly associated with AER. Conclusions Microalbuminuria in type I diabetes, which appears to represent an earlier phase in the development of clinical nephropathy, is associated with elevated blood pressure and a longer duration of diabetes.
Skin prick test reactivity to common aeroallergens in relation to total IgE, respiratory symptoms, and smoking in a general population sample of northern Italy
Authors: S. Baldacci, P. Modena, L. Carrozzi, M. Pedreschi, M. Vellutini, P. Biavati, M. Simoni, T. Sapigni, G. Viegi, P. Paoletti, C. Giuntini
Journal: Allergy (1996)
J. G. OF THE N. E. J. M.
Journal: JAMA (1962)

On Jan. 13, 1962, the Committee on Publications of the Massachusetts Medical Society celebrated the 150th anniversary of the<i>New England Journal of Medicine</i>at the Harvard Club of Boston. It was a splendidly delightful affair, with proper acclamation to John Collins Warren and James Jackson, responsible entrepreneurs for the early years of the periodical.<sup>1</sup>The title of the conservative New England creation has been changed from a provincial to an urban and back to a provincial identification.<sup>2</sup><i>"The New England Journal of Medicine and Surgery and the Collateral Branches of Science</i>.. Conducted by a Number of Physicians," first appeared as a quarterly in 1812. This was a decade before Wakley began the publication of the<i>Lancet</i>in London, a journal over the years that has been remarkably similar to the<i>New England Journal</i>. Particularly worthy of note has been the selfdetermination of the editorial policy, while at
Clinical Diagnosis.
Journal: JAMA (1897)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Horses
Authors: William R. Barclay
Journal: JAMA (1980)

Love of horses is an addiction that is every bit as compelling for some people as heroin is for others and often just as expensive. Many of us believe that the horse is nature's triumph. No more beautiful creature has graced this earth, and the horse has captured the imagination and inspired the art of many sculptors and painters. It is only natural, then, that one of today's most talented artists, Leroy Neiman, should devote much of his attention to the horse. Neiman has been sketching and painting horses for more than 30 years, and his work is to be seen in countless galleries, homes, and magazines, but for the first time we have been given the opportunity to see a major portion of his work in one magnificent volume. Neiman is obviously a "horse addict," for he depicts horses in all their beauty, grace, high action, amusing habits, and
Oral Medicine
Authors: Francis P. McCarthy, Philip L. McCarthy
Journal: New England Journal of Medicine (1955)

PigmentationNormally, one finds the oral cavity free from natural melanin pigment except in dark-complexioned Caucasians and dark-skinned races. When present, pigmentation is noted principally on the gums and the buccal mucosa and lips. Eliminating normal findings, the presence of melanin pigment in the oral cavity may suggest some constitutional disease in the body and may give the first clue to such a condition. Oral melanin pigmentation may be associated with intestinal polyposis as described by Jeghers et al.26 We have noted 4 such cases over a period of twenty years and undoubtedly overlooked others before articles on this rare . . .
The right place at the right time
Authors: J. D Cowan
Journal: BMJ (2000)

ObjectivesTo study prospectively the differences in health inequality in men and women from 1986-96 using the Office for National Statistics' longitudinal study and new socioeconomic classification.To assess the relative importance of social class (based on employment characteristics) and social position according to the general social advantage of the household to mortality risk in men and women.Design Prospective study.Setting England and Wales.Subjects Men and women of working age at the time of the 1981 census, with a recorded occupation.Main outcome measures Mortality. ResultsIn men, social class based on employment relations, measured according to the Office for National Statistics' socioeconomic classification, was the most important influence on mortality.In women, social class based on individual employment relations and conditions showed only a weak gradient.Large differences in risk of mortality in women were found, however, when social position was measured according to the general social advantage in the household.Conclusions Comparisons of the extent of health inequality in men and women are affected by the measures of social inequality used.For women, even those in paid work, classifications based on characteristics of the employment situation may give a considerable underestimate.The Office for National Statistics' new measure of socioeconomic position is useful for assessing health inequality in men, but in women a more important predictor of mortality is inequality in general social advantage of the household.
Abstract 2225: Exosomes in plasma for protein based cancer biomarkers: A clinical research tool using UHPLC-MS
Authors: David A. Sarracino, Xiaolei Xie, Courtney E. Martel, Shen Luan, Kevin Rosenblatt
Journal: Cancer Research (2019)

Abstract Introduction: Exosomes have been used as a source of biomarkers in diagnostics for many diseases, including cancer, and are now being used as therapeutic delivery systems. To date, the most efficient method for isolating exosomes from serum or plasma samples has been to use a size exclusion, chromatography (SEC) based isolation. The conditions of the SEC separation can be modified to yield extracellular vesicles of different sizes and diagnostic value. Apoptotic bodies, 50-5000nm, microvesicles, 50-1000nm, and exosomes, 30-120nm, all have different diagnostic and targeted applications. Here, we show a routine and robust method for the isolation and monitoring of proteins in exosomes isolated from plasma samples. The methods and conditions used here are focused on rapidly providing a high yield of exosome vesicles in a monodisperse 40nm size range from a plasma sample. Materials and methods: K2EDTA plasma samples from donor disease and control groups were collected with IRB approval. All SEC columns and reagents for exosome isolation were obtained as a kit (NX Prenatal, Houston, TX). The 40nm exosome fraction from the column was lysed, the proteins reduced, alkylated and digested with trypsin; the subsequent peptides were analyzed by ultra-high performance liquid chromatography (Vanquish Horizon, ThermoFisher Scientific), tandem mass spectrometry (Q-Exactive, ThermoFisher Scientific), to quantify and identify greater than 500 proteins from exosomes, isolated from a single plasma sample, in a 1 hour method. Subsequent isolations of 40nm exosome fractions were labeled with a sulfo-NHS-biotin linker, followed by lysis and enrichment with streptavidin columns, and an identical LC-MS analysis to obtain quantitative analysis of the surface membrane protein contents on the exosomes. Results: Raw data was analyzed using the label-free quantitation module in Proteome Discoverer (Thermofisher Scientific). Peptide peak areas from three technical replicate runs were used to ascertain the reproducibility of the method across both normal and disease samples. Membrane protein extracts LC-MS data was further grouped by Protein Center (ThermoFisher Scientific) by cell type and tissue of origin. Conclusions: The methods shown here provide a robust and efficient platform for 40nm exosome isolation from human plasma samples, and quantitative analysis of the protein content thereof for the purposes of biomarker discovery, quantification and screening purposes. Citation Format: David A. Sarracino, Xiaolei Xie, Courtney E. Martel, Shen Luan, Kevin Rosenblatt. Exosomes in plasma for protein based cancer biomarkers: A clinical research tool using UHPLC-MS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2225.
Diagnosis and follow-up of small hepatocellular carcinoma with selective intraarterial digital subtraction angiography
Authors: K Ikeda
Journal: Hepatology (1993)

To clarify the angiographic features of small hepatocellular carcinoma, we performed digital subtraction angiography in 91 patients with hepatocellular carcinomas of 2 cm or less. Repeated digital subtraction angiography studies were performed in 25 patients whose first angiograms showed no tumor staining. Digital subtraction angiography showed hypervascular tumor staining in only 51 patients (56.0%). We found that the smaller a tumor nodule was, the lower the detection rate of tumor stain on digital subtraction angiography. The detection rate of hypervascularity was closely correlated with the grading of histological differentiation of the tumors: well-differentiated hepatocellular carcinomas more often showed negative tumor staining. Repeated digital subtraction angiography studies showed alteration of tumor staining from isovascular to hypervascular in 6 of 6 patients with tumors that became larger than 2 cm and in 12 of 19 patients with tumors that remained 2 cm or smaller. Conversion of vascularity is commonly found in the early stage of small hepatocellular carcinoma, and the process is usually slow, taking approximately 1 yr. (HEPATOLOGY 1993;17:1003–1007.)
Cost effectiveness of immune checkpoint inhibitors in NSCLC according to PD-L1 expression.
Authors: Pedro Nazareth Aguiar, Hakaru Tadokoro, CARMELIA MARIA NOIA BARRETO, Ilka Lopes Santoro, Ramon Andrade De Mello, Hani M. Babiker, Kiran Avancha, Gilberto Lopes
Journal: Journal of Clinical Oncology (2016)

9033 Background: Immune checkpoint inhibitors are active in the treatment of NSCLC. Expression of PDL1 is being studied as a predictive biomarker. This study aimed to evaluate the cost-effectiveness of nivolumab and pembrolizumab with and without the use of PDL1 as a biomarker. Methods: We performed a systematic literature review of online databases and oncology conference presentations. All studies that assessed PDL1 expression as a biomarker were included regardless of the design of the trial, agent used, tumor histology or number of previous treatments. After that, a decision-analytic model was developed to determine the cost-effectiveness of PDL1 testing and second-line treatment with the two FDA-approved agents, nivolumab and pembrolizumab, versus docetaxel. The model used outcomes data from RCT and drug acquisition costs from the United States, using a Medicare perspective. Published utilities values were used. Health effects were expressed as quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. Results: 14 studies (4 of which were randomized) with 2,700 patients were retrieved and included in the model. PDL1 expression was associated with a greater likelihood of response (RR 2.08; CI: 1.49-2.91), and this effect was more intense among non-SQ tumors (RR 3.13; CI: 2.15-4.54) than among those with SQ histology (RR 2.12; CI: 1.37-3.29). Moreover, the ORR was proportional to the cutoff value ranging from 19% when using 1% to 54% with a cutoff of 75%. PDL1 expression was also associated with better PFS (HR 0.83; 95% CI: 0.74-0.93) and a better OS (HR 0.86; 95% CI: 0.76-0.97). Regarding cost-effectiveness, PDL1 ≥ 1% improved incremental QALY of nivo vs. doce for patients with non-SQ tumors by 67%, (from 0.124 to 0.208) leading to a 40% reduction in the ICER (from US$ 176K to US$ 105K). Interestingly, this effect was not observed among patients with SQ tumors. For pembro, using a 50% instead of a 1% cutoff increased the incremental QALY by18% (from 0.138 to 0.164) leading to a 15% reduction in ICER (from $ 163K to $ 138K). Conclusions: Use of PDL1 expression as a biomarker may increase the cost-effectiveness of treatment with immune checkpoint inhibitors and further validation is warranted.
Bureau of Investigation
Journal: JAMA (1946)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal